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T Cells: A Mechanism for the Loss of T Cells in Patients with Pulmonary Tuberculosis1
*
Department of Microbiology, University of Pennsylvania School of Medicine, and
Division of Pulmonary Medicine and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany;
§
Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias, Mexico, Mexico City; and
¶
Microbiology and Immunology Department, Gazi University, Ankara, Turkey
Although the identity of T cells involved in the protection against
Mycobacterium tuberculosis (Mtb) in humans remain
unknown, patients with pulmonary tuberculosis (TB) have reduced numbers
of Mtb-reactive, V
9+/V
2+ T cells in their
blood and lungs. Here we have determined whether this T loss is
a consequence of Mtb Ag-mediated activation-induced cell death (AICD).
Using a DNA polymerase-mediated dUTP nick translation labeling assay,
5% or less of freshly isolated CD4+ 
ß or T
cells from normal healthy individuals and TB patients were apoptotic.
However, during culture Mtb Ags induced apoptosis in a large proportion
of V9+/V2+ peripheral blood T cells from
healthy subjects (30–45%) and TB patients (55–68%); this was
increased further in the presence of IL-2. By contrast, anti-CD3
did not induce any significant level of apoptosis in T cells
from healthy subjects or TB patients. Mtb Ag stimulation rapidly
induced Fas and Fas ligand (FasL) expression by T cells, and in
the presence of metalloproteinase-inhibitors >70% of T cells
were FasL+. Blockade of Fas-FasL interactions reduced the
level of Mtb-mediated T cell apoptosis by 75 to 80%.
Collectively, these findings demonstrate that Mtb-reactive T
cells are more susceptible to AICD and that the Fas-FasL pathways of
apoptosis is involved. AICD of T cells, therefore, provides an
explanation for the loss of Mtb-reactive T cells during mycobacterial
infection.
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